Cancer Screening Notes

How is Cancer Diagnosed? Cancer Screening Module

Introduction

This lecture series focuses on how cancer is diagnosed, covering:

• Screening methods

• Clinical history, signs, and symptoms

• Radiology

• Pathology

Objectives

By the end of this lecture, you should understand:

• The principles of cancer screening.

• Awareness that some cancers will be detected through screening.

• An outline of the main cancer screening programmes in the UK, their principles, and utility.

Cancer Burden

• One in three people will be diagnosed with cancer during their lifetime.

• Cancer mostly affects older people; 65% of cases occur in those over 65.

• In 2000, more than 270,000 new cases of cancer were registered in the UK.

• Lung, breast, prostate, and colorectal cancers account for over half of all cases diagnosed.

Key Features of Screening

• Tests are done among apparently WELL people to identify those at an increased risk of cancer.

• Identification of unrecognized disease.

• Distinguish those probably with the disease from those who probably don’t.

• Screening test is NOT diagnostic.

• Suspicion of disease must be referred for diagnosis and treatment.

Screening Questions

• Why screen?

• Which cancers are screened?

WHO Screening Principles (Wilson & Junger, 1968)

• The condition should be an important health risk.

• The natural history should be well understood.

• Recognizable early stage.

• Early treatment should be beneficial.

• There should be a suitable test.

• The test should be acceptable.

• Adequate facilities for diagnosis and treatment.

• Repeat screening at intervals for diseases of insidious onset.

• Physical and psychological harm should be less than the benefit of detection.

• Costs should be balanced against benefits.

Measuring Test Performance

Test Accuracy

• Does it distinguish between disease or not?

• Are patients with certain test results more likely to have the target disorder than patients with other test results?

• Labels patient.

• Determines treatment.

Frequency

• Ideal test: More positive results in diseased individuals.

Variation in Population

• Cut-off point indicating the degree of "positivity" differentiates between non-diseased and diseased individuals.

Basic Table for Calculating Diagnostic Values

Sensitivity

• Percentage of patients with disease who test positive.

• Example:

• Sensitivity formula: $Sensitivity = TP / (TP + FN)$

Specificity

• Percentage of patients without disease who test negative.

• Example:

• Specificity formula: $Specificity = TN/ (TN + FP)$

Positive Predictive Value (PPV)

• Percentage of patients with a positive test who actually have the disease.

• Example:

• Positive predictive value formula: $PPV = TP / (TP + FP)$

Positive Predictive Value Example

Example:

1. 38/40 = 95%

2. 38/44 = 86%

3. 54/56 = 96%

4. 54/60 = 90%

• Definition of PPV:

Negative Predictive Value (NPV)

• Percentage of patients with a negative test who do not have the disease.

• Negative predictive value formula: $NPV = TN / (TN + FN)$

Prevalence

Does Prevalence Influence Test Accuracy?
Prevalence (%): $Prevalence ($

Prevalence of 15%

Prevalence of 15% - Example Values

Sensitivity 95%
Specificity 95%

Prevalence of 5%

Sensitivity 95%
Specificity 95%

Impact of Prevalence

Sensitivity 95%
Specificity 95%

Screening Effectiveness & the Natural History of Disease

Screening shifts detection from symptomatic presentation to an earlier stage, before metastatic spread.

• Early

• Screen Detected

• Symptomatic presentation

• Metastatic spread

• Late

Screening Effectiveness

Screening shifts detection from symptomatic presentation to an earlier stage, before metastatic spread.

• Early

• Screen Detected

• Symptomatic presentation

• Metastatic spread

• Late

Screening Effectiveness

Screening shifts detection from symptomatic presentation to an earlier stage, before metastatic spread.

• Early

• Screen Detected

• Symptomatic presentation

• Metastatic spread

• Late

The Ideal Screening Test

• Simple

• Cheap

• Easily repeatable

• Easy and unambiguous to interpret

• No false positives

• No false negatives

• Acceptable

• Benefits outweigh the harms

A Successful Screening Programme: Other Factors

• Training

• Education

• Mass awareness

• Quality assurance (incl. Key performance Indicators)

• Finances

Screening: The Downside

• Labels a person as an increased risk of cancer

• Psychological impact

• Impact of turnaround times

• Success depends on uptake (education/training/feasibility)

• Impact of social media

• Financial considerations for people attending screening

Major UK Cancer Screening Programmes

Breast Cancer Screening

Age Specific Incidence and Mortality for Breast Cancer in UK

(Graph illustrating incidence and mortality rates vs. age)

Breast Cancer Screening

• Finds unsuspected disease

• Divides women into two categories:

  • Normal

  • Potential breast cancer

• Identifies those needing further assessment

Mammographic Screening

Mammographic screening is the only technique which has been shown to reduce breast cancer mortality in the population.

The NHS Breast Screening Programme

• Provides mammographic screening for all women of 50 and over (50 - 70 by invitation), repeated every three years

• Includes a fully funded training programme

• All mammograms are double-read (by at least one Consultant Radiologist)

Mammography

Normal Mammogram

(Image of a normal mammogram)

Abnormal Mammogram

(Image of an abnormal mammogram)

• Picks up lumps

• Picks up calcification including micro-calcification

Two-view Mammography in Screening for Breast Cancer

• Programmes using two-view mammography detected:

  • 42% more small (<15 mm) invasive cancers

  • 3% more in situ cancers (esp. high grade)

• Two-view mammography is recommended at all screening visits

Next Steps

• Abnormal mammogram is followed by a biopsy for a diagnosis

• MDT (multi-disciplinary team) discussion is vital for correlations

NHS Cervical Screening Programme

Call Recall System - 1966 & 1988

Natural History of the Disease: Risk Factors

• Human Papilloma Virus infection (high risk serotypes 16, 18, 31, and 33)

• HPV changes

Natural History of the Disease: Disease has a Pre-Invasive Phase

CIN1, CIN2, CIN3, Invasive

Amenable for Screening

Cervical intraepithelial neoplasia (CIN) arises within the transformation zone.

Cervical Screening Programme

• Not a test for cancer.

• It is a method of preventing cancer by detecting and treating early abnormalities which, if left untreated, could lead to invasive cancer.

• The first stage in cervical screening is taking a sample for use in HPV primary screening (2020) and liquid-based cytology (LBC) [phased in Oct 2008].

• A sample of cells is taken from the cervix for analysis. A doctor or nurse inserts an instrument (a speculum) to open the woman's vagina and uses a spatula to sweep around the cervix.

• Early detection and treatment can prevent 75 percent of cancers developing.

Cervical Screening: Call Recall System

• All women between the ages of 25 and 64 are eligible for a free cervical screening test every three to five years.

• The screening intervals are:

  • Age group (years) Frequency of screening

  • 25 First invitation

  • 25 - 49 3 yearly

  • 50 - 64 5 yearly

  • 65+ Only screen those who have not been screened since age 50 or have had recent abnormal tests

• The NHS call and recall system invites women who are registered with a GP. It also keeps track of any follow-up investigation, and, if all is well, recalls the woman for screening in three or five years' time.

Changes to the Cervical Screening Programme – High-Risk HPV Testing (as of Jan 2020)

Now the 1st test on the sample, followed by cytology triage (liquid-based cytology).

Primary HPV Screening

• HPV primary screening uses HR-HPV (high-risk HPV) testing as the first test on the cervical screening sample.

• Cytology becomes the triage test, only used when we find HR-HPV.

• The same laboratory performs both tests and issues a single report with all results.

The Borderline Smear (HPV Changes)

Mild Dyskaryosis Severe Dyskaryosis

3. 6m women screened annually

4. 7% considered moderate or severe

Next Steps

Abnormal HPV triage is followed by an LBC; if abnormal: biopsy for diagnosis.

NHS Bowel Cancer Screening Programme

#

The majority of bowel cancers (between 70% and 90%) develop from benign adenomatous polyps lining the bowel wall. The adenoma–adenocarcinoma sequence, in which the benign polyp develops into bowel cancer, takes approximately 10 years (although it may be as long as 15 years before symptoms develop). Amenability for screening

#

Bowel cancer screening aims to detect bowel cancer at an early stage (in people with no symptoms), when treatment is more likely to be effective: looks for occult blood in the stool. Bowel cancer screening can also detect polyps. These are not cancers, but may develop into cancers over time. Polyps can easily be removed, reducing the risk of bowel cancer developing. Aims of the programme.

#

The cohort screened. Bowel cancer screening is offered every 2 years to men and women aged 60 to 74. People older than this can ask for a screening kit every 2 years. An additional one-off test called bowel scope screening is being introduced in England for men and women at the age of 55. https://www.gov.uk/guidance/bowel-cancer-screening-programme-overview.

The FIT Test

Faecal Immunochemical Test: which uses antibodies that specifically recognise human haemoglobin [contrast: gFOB recognises haem component of any haemoglobin: tests for pseudo-peroxidase activity]. FIT advantages – detects only human blood – Associated with higher programme uptake – Objective numerical result [therefore increased sensitivity] – Only one sample required – More sensitive than gFOB.

The FIT Test

The gFOB Test

This past screening test is a guaiac test in which the participant smears small samples of stool (from three separate bowel motions) on to the FOB test card. The test card has three ‘windows’ (two ‘spots’ in each window are used per bowel motion) for the participant to place his or her smear. The sensitivity of the FOB test is improved by performing it on three separate occasions as bowel cancer (and bowel polyps) bleed intermittently.

Bowel Scope Screening

Bowel scope screening: for people aged 55 where a thin, flexible tube with a camera at the end is used to look inside the bowel [flexible sigmoidoscopy or "flexisig“]. If you decide not to have the test straight away, you can have it at any point up to your 60th birthday. From 60 onwards: invited to do a bowel cancer screening home test kit every 2 years instead.

Next Tests: After Abnormal FIT test

Colonoscopy and biopsy interpretation
Double contrast barium enema

NHS Bowel Screening Programme

(www.cancerscreening.nhs.uk/bowel/)

Screening for Prostate Cancer

Equal rights: Women have breast and cervical cancer screening, should men have prostate cancer screening?

PSA Test

• Prostate-Specific Antigen

• Organ-specific

• A product of prostatic epithelium

• Minute amounts found in serum

• Normal range 0-4ng/ml

How Useful is Raised PSA?

PSA +ve:

• Cancer

  • Tumours of large volume

  • Well differentiated

  • 80% of those with cancer have PSA levels > 4.0 ng/ml

• Benign Prostatic Hyperplasia

  • 25-30% of men with BPH have PSA levels > 4.0 ng/ml

• Acute Prostatitis

• Exercise/sexual activity

How Useful is Low PSA?

PSA –ve: 20-40% of patients with organ-confined prostate cancer have a PSA of ≤ 4.0 ng/ml. PSA testing is therefore neither sensitive nor specific.

The Current Stance

There is no organized screening program for prostate cancer but an informed choice program. The Prostate Cancer Risk Management program (September 2002).

• Counselling for those (aged 50 and over) who request screening

• Leaflet giving pros and cons of PSA test and treatment options

• Informed choice

Summary

• The WHO principles of screening should apply to any cancer screening test.

• Demand good quality evidence of reproducibility, accuracy, and effectiveness before a new screening test is introduced.

• Screening tests are not diagnostic of cancer.

• Breast cancer screening: Double-view Mammogram

• Cervical cancer screening: HPV screen and LBC triage

• Bowel cancer screening: FIT test

Further Reading

• http://www.cancerscreening.nhs.uk/ (info on breast, cervical, and colorectal screening)

• http://http://www.cancerresearchuk.org/ (basic info about different cancers)

• Uses and abuses of screening tests. Grimes DA and Schulz KF. Lancet 2002; 359: 881-884

• Women need better information about routine mammography. Thornton H, Edwards A and Baum M. BMJ 2003; 327: 101-103

Contacts

Dr. A Mukherjee
abhik.mukherjee1@nottingham.ac.uk
NMPN